Exploring Aromatic Donor-Acceptor Interactions in Water

描述(申请人提供)：但我们能让它在水中工作吗？化学家们现在正在探索超越共价键的分子结构的设计。从自然中获得灵感，折叠或自组装的分子是从基本原理设计出来的。创建在水中折叠和组装的分子系统目前是一个重大挑战，尽管一旦创建，这种系统将能够以前所未有的方式与生物结构和分子相互作用。我们早期的Folamer研究证实，芳香族给体-受体相互作用可以用作水中非常强的稳定相互作用，产生折叠、堆积结构(Lokey和Iverson，Nature，1995,375,303-5)。叫做伊达默斯。最近，我们已经有了令人兴奋的发现，富含电子的芳香族单元链将专门识别水溶液中缺乏电子的芳香族单元链的互补链，从而形成稳定的双链(Gabriel和Iverson，J.化学。社会团体，2002年，124年，15174-15175。这项提议的前两个具体目标描述了在水中利用富电子的1，5-二烷氧基萘(DAN)和缺乏电子的1，4，5，8-萘四甲酸二亚胺(NDI)芳香族部分的稳定和识别能力的新型折叠和组装分子体系的创建和表征。后三个具体目标采取下一个关键步骤，探索与生物分子的不同相互作用策略。 从基础科学到实际应用，我们将1)研究一种全新的类似于核酸发夹的Aedamer折叠拓扑结构，2)利用Dan-NDI相互作用的识别能力从较小的折叠片段制备大分子组件，3)研究Dan-NDI相互作用在蛋白质疏水核心中作为稳定力的作用，4)基于对基于NDI的低聚物的核磁共振分析得出的结构，创建下一代线状DNA多嵌入体，以及5)使用噬菌体展示技术分离具有高亲和力和特异性的多肽，用于结合NDI残基链，以便在生物医学和生物技术应用中潜在地应用。

DESCRIPTION (provided by applicant): But can we make it work in water? Chemists are now exploring the design of molecular architectures that extend beyond covalent bonding. Taking inspiration from Nature, molecules that fold or self-assemble are being designed from first principles. Creating molecular systems that fold and assemble in water is currently a major challenge, although once created, such systems will be able to interact with biological structures and molecules in unprecedented ways. Our early foldamer studies verified that aromatic donor-acceptor interactions can be used as a remarkably strong stabilizing interaction in water, producing folded, stacked structures (Lokey and Iverson, Nature, 1995, 375, 303-5.) called aedamers. More recently, we have made the exciting discovery that chains of electron rich aromatic units will specifically recognize a complementary chain of electron deficient aromatic units in aqueous solution to form a stable duplex (Gabriel and Iverson, J. of the Am. Chem. Soc., 2002, 124, 15174-15175.). The first two specific aims of this proposal describe the creation and characterization of novel folding and assembling molecular systems that in water exploit the stabilizing and recognition abilities of the electron rich 1,5-dialkoxynaphthalene (DAN) and the electron deficient 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) aromatic moieties. The last three specific aims take the next critical step and probe different interaction strategies with biological molecules. Spanning the range from basic science to practical application, we will 1) investigate an entirely new aedamer folding topology analogous to nucleic acid hairpins, 2) use the recognition ability of the DAN-NDI interaction to produce large molecular assemblies from smaller folding pieces, 3) investigate the utility of DAN-NDI interactions as a stabilizing force in a protein hydrophobic core, 4) create next-generation threading DNA poly-intercalators based on structures derived from NMR analysis of our NDI-based oligomers, and 5) use phage display to isolate a peptide with high affinity and specificity for binding a chain of NDI residues for potential use in biomedical and biotechnological applications.